Basic physico-chemical properties: from colorless to slight yellow tinged clear syrup.
Cough and cold preparations. Mucolytics. ATC code R05C B06.
The active substance of Abrol® syrup – ambroxol hydrochloride – increases secretion of glands of glands in the airways. Ambroxol increases the secretion of pulmonary surfactant by direct effect on type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates a ciliary activity. This leads to increased mucus secretion and improves the mucociliary clearance.
Activation of fluid secretion and increased mucociliary clearance facilitate mucus excretion and reduce cough.
Ambroxol hydrochloride is known to have local anesthetic effect, which may be explained by its ability to block sodium channels. Blocking of neuronal sodium channels was characterized by the fact that the binding was reversible and concentration-dependent.
Ambroxol hydrochloride has anti-inflammatory effect, since it significantly reduces the release of cytokine from blood and tissue binding of mononuclear and polymorphonuclear cells.
There are data that in patients with pharyngitis, the use of ambroxol hydrochloride helped to significantly reduce pain and redness in the throat. It is also known that ambroxol hydrochloride is effective in treatment of the upper respiratory tract since it promotes rapid relive of pain and associated discomfort in the nasal cavity, in the area of the ear and trachea during inhaling.
After using ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin) in bronchopulmonary secretion and expectorationincrease.
Absorption. Absorption of ambroxol hydrochloride from the non-sustained-release oral forms is rapid and almost complete, with linear dependence in therapeutic range. The maximum plasma levels are reached
after 1-2.5 hours when taking orally fast release pharmaceutical forms and on average after 6.5 hours when using sustained releaseforms.
Distribution. In oral administration, the distribution of ambroxol hydrochloride from blood to tissue is strongly pronounced, with the highest concentration of the active substance in the lungs. The distribution volume in oral administration is about 552 l. In the blood plasma within the therapeutic range, about 90% of the drug is bound to theproteins.
Metabolism and excretion. Approximately 30 % of the dose after oral administration is eliminated by presystemic metabolism. Ambroxol hydrochloride is metabolized mostly in the liver by glucuronidation and decomposition to dibromanthranilic acid (approximately 10% of the dose). It is known that in human liver microsomes CYP3A4 is responsible for ambroxol hydrochloride metabolism to dibromanthranilic acid.
Within 3 days of oral administration about 6 % of dose is excreted in unchanged from, whereas about 26% of dose is excreted in conjugated form with theurine.
The plasma half-life is about 10 hours. Total clearance is within 660 ml/min together with renal clearance, which is about 8 % of the totalclearance.
Pharmacokinetics in special populations of patients. In patients with liver dysfunction, elimination of ambroxol hydrochloride is reduced, that causes a 1.3-2-fold higher level in the blood plasma. Since the therapeutic range of ambroxol hydrochloride is quite wide, dose adjustment is not required.
Age and sex have no clinically significant effect on the pharmacokinetics of ambroxol hydrochloride; therefore, dose adjustment is not required.
Food intake has no effect on the bioavailability of ambroxol hydrochloride.
Secretolytic therapy in acute and chronic bronchopulmonary diseases, associated with impaired bronchial secretion and weakening of mucus movement
Abrol®, syrup, 15 mg/5 ml, cannot be used in patients with hypersensitivity to ambroxol hydrochloride or the other components of the drug.
There have been only several reports about severe skin lesions: Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), associated with the use of expectorants, such as ambroxol hydrochloride. In most cases they could be explained by the severity of the main disease and/or concomitant use of other preparation. Also, at the initial stage of Stevens-Johnson syndrome or Lyell's syndrome, patients may have non-specific flu-like symptoms, such as fever, aches, rhinitis, cough and sore throat. In case of such non-specific flu-like symptoms it is possibly to use symptomatic treatment with drugs against cough and cold by mistake. Therefore, in case of new lesions of skin or mucous membranes, seek medical attention and discontinue treatment with ambroxol hydrochloride immediately. In case of violation of bronchial motility and increased mucus secretion (e.g. in such rare disease as primary ciliary dyskinesia) the drug Abrol® syrup, 15 mg/5 ml, should be used with caution, since ambroxol may increase mucussecretion.
Patients with impaired renal function or severe hepatic insufficiency should take Abrol® syrup, 15 mg/5 ml, only after consulting their doctor. When using ambroxol, as well as any substance that is metabolized in the liver and then excreted by the kidneys, the accumulation of metabolites formed in the liver occurs in patients with severe renalinsufficiency.
Abrol® syrup, 15 mg/5 ml, contains 1.225 g of sorbitol in 5 ml (equivalent to 4.9 g when using the maximum recommended daily dose). If you have a known intolerance to some sugars, consult your physician before taking this medicinal agent.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of the drug Abrol® syrup, 15 mg/5 ml, and drugs that suppress cough, may lead to excessive accumulation of mucus due to the inhibition of the cough reflex. Such combination is possible only after careful evaluation by the doctor of the ratio of the expected benefit and risk of the use.
Peculiarities of use.
Use during pregnancy or breast-feeding.
Pregnancy. Ambroxol hydrochloride penetrates the placental barrier.
No adverse effects on the fetus have been detected when using the drug after the 28th week of pregnancy. However, usual precautions should be taken when using drugs during pregnancy. Especially during the I trimester of pregnancy it is not recommended to use Abrol®.
Breast feeding. Ambroxol hydrochloride penetrates the breast milk. Abrol® syrup, 15 mg/5 ml, is not recommended for use during the period of breast-feeding.
Effects on ability to drive and use machines.
There are no data regarding the influence on the reaction rate when driving or operating machinery. No studies have been conducted.
Dosage and administration.
Unless otherwise prescribed, the recommended dosage regimen fir the drug Abrol® syrup, 15 mg/5 ml, is as follows:
children less than 2 years old: 2.5 ml (1/2 tea spoon) 2 times per day (equivalent to 15 mg of ambroxol hydrochloride perday);
children 2-6 years old: 2.5 ml (1/2 tea spoon) 3 times per day (equivalent to 22.5 mg of ambroxol hydrochloride perday);
children 6-12 years old: 5 ml (1 tea spoon) 2-3 times per day (equivalent to 30-45 mg of ambroxol hydrochloride perday);
adults and children more than 12 years old: the dose is 10 ml (2 tea spoons) 3 times per day (equivalent to 90 mg of ambroxol hydrochloride per day) during the first 2-3 days and then 10 ml (2 tea spoons) 2 times per day (equivalent to 60 mg of ambroxol hydrochloride perday).
If necessary, the therapeutic effect for adults and children more than 12 years old may be enhanced by increasing the dose to 20 ml 2 times per day (equivalent to 120 mg of ambroxol hydrochloride per day).
For adults and children more than 12 years old, it is recommended to use syrup with higher concentration (Abrol® syrup, 30 mg/5 ml).
Abrol® syrup, 15 mg/5 ml, may be used regardless of the food intake. Abrol® syrup, 15 mg/5 ml, may be measured by the dosing cup that is supplied with the product.
In general, there are no restrictions regarding the duration of use, but prolonged therapy should be conducted under medical supervision.
Abrol® syrup, 15 mg/5 ml, should not be used more than 4-5 days without consulting a doctor.
Abrol® syrup, 15 mg/5 ml, may be used in patients with diabetes mellitus. 5 ml contain 1.225 g of carbohydrates.
Abrol® syrup, 15 mg/5 ml, does not contain alcohol.
The drug may be used in pediatric practice. Use in children less than 2 years old by according to the doctor’s prescription.
As of today, there are no reports on specific symptoms of overdose. The symptoms known from the rare reports on cases of overdose and using the drug by mistake correspond to the known adverse effects of Abrol® syrup, 15 mg/5 ml, in the recommended doses and require symptomatic treatment.
Immune system, skin and subcutaneous tissue disorders: skin rash, urticaria, angioedema, pruritus, anaphylactic reactions (including anaphylactic shock), other hypersensitivity reaction, erythema, severe skin lesions: Stevens - Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).